Existing evidence suggests that vasopressin (VP, antidiuretic hormone) release is elevated in several types of experimental hypertension as well as in humans with hypertension. This situation exists in rats genetically disposed to spontaneous development of hypertension (e.g. the spontaneously hypertensive rats (SHRs) developed by Okamoto), but the factors responsible for elevated VP secretion have not been delineated. Therefore, we propose to compare the regulation of VP release in SHRs with that in normotensive control rats of the Wistar-Kyoto strain. Three experimental approaches will be utilized to evaluate regulation of VP release in these studies: 1) In vivo experiments will be performed in which VP and renin release are evaluated following manipulation of the volume and osmolality of the extracellular fluid and of arterial blood pressure. These experiments will be performed on rats of various ages to allow assessment of alterations in the control of the two neuroendocrine systems involved in regulation of fluid and electrolyte balance at different stages of the development of hypertension. 2) In vitro experiments will be performed to compare VP release from hypothalamo-neurohypophyseal explants obtained from SHRs and normotensive rats. VP release in response to agents which are known to alter VP release from such explants will be tested (e.g. osmotic stimuli, acetylcholine, norepinephrine, and angiotensin II). 3) A potential morphological basis for cardiovascular regulation of VP release will be explored with histochemical analysis of interactions between VP neurons and brainstem (afferent) catecholamine systems in order to evaluate whether alterations in the catecholaminergic innervation of VP neurons is responsible for abnormalities of VP release observed in the SHR. These studies will employ quantitative techniques for simultaneous visualization of catecholamines and VP in a single tissue sample.